Aryl allyl sulfones

ABSTRACT

Aryl allyl sulfones of the formula WHEREIN Ar is phenyl optionally substituted with lower alkyl, lower alkoxy, halomethyl, nitro or halogen and HA has the formula WHEREIN R&#39;&#39;1 is hydrogen or lower alkyl and FORM FLUORENE OR SATURATED OR UNSATURATED CYCLOALKYL OF THREE TO SEVEN CARBON ATOMS OPTIONALLY SUBSTITUTED WITH ONE OR MORE LOWER ALKYL AND/OR LOWER ALKOXY USEFUL AS INTERMEDIATES IN THE PREPARATION OF CYCLOPROPANECARBOXYLIC ACID ESTERS HAVING INSECTICIDAL ACTIVITY.

United States Patent 91 Martel et al.

ARYL ALLYL SULFONES Inventors: Jacques Martel, Bondy 93; Chanh l-luynh,Villemombie 93, both of France Assignee: Roussel-Uc Lat, Paris, FranceFiled: Dec. 16, 1969 Appl. No.: 885,634

Related US. Application Data Division of Ser. No. 662,278, Aug. 22,1967, abandoned.

Foreign Application Priority Data Augv 26, 1966 France ..6674404 Aug.26, 1966 France ..6674405 Feb. 24, 1967 France ..6796425 June 16, 1967France ..67l10719 July 19, 1967 France ..67114833 US. Cl. ..260/607 A,260/326.3, 260/345. 1

260/3461, 260/347.4, 260/468 R, 260/469 R, 260/470, 260/501 .17, 260/514R, 260/515, 260/544.6, 260/544 R, 260/546, 260/617 R, 260/618 R, 260/638R, 260/648 R, 260/649 D, 260/654 R, 424/305, 424/308,

[45] Jan. 16, 1973 Primary Examiner-Lewis Gotts Assistant Examiner-D. R.Phillips Attorney-Hammond & Littell ABSTRACT Aryl allyl sulfones of theformula wherein Ar is phenyl optionally substituted with lower alkyl,lower alkoxy, halomethyl, nitro or halogen and HA has the formulawherein R is hydrogen or lower alkyl and form fluorene or saturated orunsaturated cycloalkyl of three to seven carbon atoms optionallysubstituted with one or more lower alkyl and/or lower alkoxy useasintermediates in the preparation of cyclopropanecarboxylic acid estershaving insecticidal activity.

7 Claims, N0 Drawings ARYL ALLYL SULFONES PRIOR APPLICATION Thisapplication is a divisional application of copending application Ser.No. 662,278 filed Aug. 22, 1967, now abandoned.

OBJECTS OF THE lNVENTlON THE INVENTION The novel cyclopropanecarboxylicacids and esters of the invention have the structure of the formulawherein Z, and Z are selected from the group consisting of hydrogen,alkyl, aralkyl, aryl, alkenyl non-conjugated with the cyclopropane ring,alkynyl non-conjugated with the cyclopropane ring, cycloalkyl,cycloalkenyl and heterocyclic; R is selected from the group consistingof OH and OR in which R is selected from the group consisting of loweralkyl which may be substituted, benzyl which may be substituted on thephenyl or methylene portion, N-methylene-dicarboximide, (5-benzyl-furyl-3) methyl, and a cyclopentene of the formula CH3 R whereinR is selected from the group consisting of alkyl, alkynyl, alkenyl,aryl, aralkyl, cycloalkyl, cycloalkenyl and heterocyclic; A is abivalent allyl radical selected from the group consisting of wherein R,is selected from the group consisting of hydrogen and lower alkyl, R:and R are selected from the group consisting of alkyl, alkynyl, alkenyl,aryl, aralkyl, cycloalkyl, cycloalkenyl and heterocyclic and takentogether with the carbon atom to which they are attached form a ringselected from the group consisting of carbon homo rings and unsaturatedcarbon homo rings of 3 to 7 carbon atoms and heterocyclic rings whichmay be substituted with lower alkyl or lower alkoxy and R and R maytogether form a polycyclic aromatic radical, R4 is lower alkyl, R isselected from the group consisting of hydrogen and lower alkyl and R4and R5 together with the carbon atoms to which they are attached mayform a saturated or unsaturated carbon homo ring or a heterocyclic ring,Y is selected from the group consisting of methylene and a saturated orunsaturated carbon chain and Y is selected from the group consisting ofmethine and a saturated or unsaturated carbon chain with the provisothat when Z, and Z are methyl and R is hydrogen, R is other than methyland are important compounds. The free acids (where R OH) can beesterified with or converted into a functional derivative thereof whichcan be esterified with, an alcohol of the formula HOR' to obtain thecorresponding esters which have insecticidal properties and ananthelmintic activity.

The esters of Formula I in which R is 2-R"-3-methyl-l-oxo-2-cyclopentehe-4-yl wherein R" has the above definition areparticularly distinguished by a strong insecticidal activity and a lowtoxicity to humans and warm blooded animals. Examples of said esters arethose wherein R" is allyl, cis-2-butenyl, cis-2,4-pentadenyl,2-cyclopentenyl, cyclohexyl, 2-cyclohexenyl, Z-propynyl andZ-furyl-methyl.

The following esters of Formula l have been found to possess a markedinsecticidal activity: the d,l-allethrolone esters of d,l-trans3,3-dimethyl-2-(2-ethyl- 1'-butentyl)-cyclopropanecarboxylic acid,d,l-trans 3,3-dimethyl-2-cyclopentylidenemethylcyclopropanecarboxylicacid, d,l -trans 3,3-dimethyl-2-cyclohexylidenemethyl-cyclopropanecarboxylic acid, d,l-trans3,3-dirnethyl-2-cyclopropylidene-methyl-lcyclopropanecarboxylic acid andd,l-trans 3,3 dimethyl-2-cyclobutylidenemethyl-l-cyclopropanecarboxylicacid; the cis-cinerolone ester of d,l-trans 3,3-dimethyl-2-cyclopentylidenemethyl-lcyclopropanecarboxylic acid; thel-oxo-3-methyl-2- (2-cyclohexenyl)-2-cyclopentene-4-ol ester of d,ltrans3,3-dimethyl-2-cyclopentylidenemethylcyclopropanecarboxylic acid; andthe (S-benzyl-furyl- 3)methyl alcohol ester of d,land d-trans 3,3-dimethyl-Z-cyclopentylidene-methyll cyclopropanecarboxylic acid. Thesaid esters have been found to be effective against such insects ashouse flies, grain weevils, american cockroaches, german cockroaches,yellow fever mosquitos at dosages depending onthe way they are used.More particularly they may be associated with synergists such aspiperonyl butoxide and spread by means of aerosols, spacesprays orpowders.

The novel process of the invention comprises reacting an alkali metalaryl sulfinatc of the formula ArSO M n wherein M is an alkali metal suchas sodium or potassium and Ar is an aryl radicalof one to two aromaticrings which may be substituted with at least one substituent selectedfrom the group consisting of lower alkyl, lower alkoxy, halogen, nitroand halo methyl with an allylic halogen derivative of the formula HAXIll wherein A has the above definition and X is selected from the groupconsisting of chlorine, iodine, bromine, mesyl and tosyl to form thecorresponding aryl allyl sulfone of the formula O IV wherein A and Arhave the above definitions, reacting the latter in the presence of abasic agent with an 01,13- ethylenic ester of the formula wherein A, R,Z, and Z2 have the foregoing definition, hydrolyzing the latter underalkaline conditions to form the corresponding free acid, preferablyconverting the latter into a functionafderivative such as acid halide,anhydride, mixed anhydride, ester or metal salt, reacting the functionalderivative or the free acid with an alcohol of the formula wherein R hasthe foregoing definition and N is selected from the group consisting ofhydroxy and halide to form the corresponding ester of Formula l.

The process of the invention has the advantage of simplicity since itsynthesizes a substituted cyclopropane in a single step from readilyavailable raw materials or from materials which can be prepared withoutany great difficulty and the process can be operated without anyhazards. Known methods of producing cyclopropanecarboxylic acids ortheir esters require the preparation and use of relatively unstablediazo compounds such as diazoacetonitrile or diazoacetic acid esters orto avoid this hazard required a multiple step process having rather pooryields in some steps.

Another advantage of the process of the invention is the general naturethereof whereby a large variety of differently substituted compounds maybe made. in the aryl allyl sulfones of Formula TV, for example, the arylgroup may be homo or polycylic and may be substituted with numerousdifferent substituents, the ptolyl group furnishing particularlyexcellent results. More important, the allyl group of the aryl allylsulfone can have most varied structures and may be of the linear typesuch ast: (vii-Arm wherein R and R may be, for example, ethyl,isopropyl, phenyl, cycloalkyl or together may form a five carbon ring ora heterocyclic or the cyclic type such as wherein R may be alkyl.

The process of the invention is so general that the aryl allyl sulfoneof Formula IV may not only be reacted with an ester of Formula V butalso with other a,B-ethylenic carbonyl compounds such as ketones,nitriles and conjugated amides to form the correspondingcyclopropanecarboxylic acid ester.

The preparation of the aryl allyl sulfones of Formula IV is preferablyeffected in a solvent such as a methanol or ethanol medium in thepresence of a basic agent such as alkali metal carbonates or acetates.Preferably, the said reaction is effected in methanol in the presence ofsodium or potassium carbonate.

As a modification of the process, the aryl allyl sulfones can beprepared by reacting an alkali metal aryl sulfinate with an alcohol ofthe formula wherein A has the above definition in the presence of formicacid or by the method described in French Patent No. 1,483,715.

The alkali metal aryl sulfinates of Formula II can be prepared by knownprocesses such as reduction of aryl sulfonyl chlorides to arylsulfinicacids which are converted into the corresponding alkali metal salts. Theacrylic acid esters of Formula V are prepared also by knownmethods andare preferably the lower alkyl esters such as methyl, ethyl or n-butyl.

The reaction of the aryl allyl sulfone and the allylic ester of FormulaV is effected in an anhydrous organic medium in the presence of a basicagent, preferably an alkali metal amide, hydride or alcoholate or dimsylsodium. Particularly advantageous basic agents are sodium methylate,sodium tert -amylate and potassium tert.-butylate. The organic solventmay be selected from the group consisting of aromatic hydrocarbons suchas benzene, toluene, etc.; others such as tetrahydrofuran; andpreferably aprotic dipolar solvents such as dimethylformamide,dimethylsulfoxide, hexamethylene-phosphoramide or acetonitrile. The mostpreferred process is reacted in tetrahydrofuran in the presence ofpotassium tert.-butylate or in benzene in the presence of sodiumtert.-amylate or in dimethylformamide in the presence of potassiumtert.-butylate or in dimethylsulfoxide in the presence of sodiummethylate or in dimcthylsulfoxide in the presence of potassiumtert.-butylate.

An additional advantage of the process of the invention occurs when Ahas the structure the compound of Formula I being of the spiro type, thetwo theoretically possible isomers can be isolated and these isomershave been designated as the cis isomer and and the trans isomer. Theymay be represented as follows:

Trans isomer dis isomer Z1 k -COR \7--CO-R Z 2 Y I Y Although it is notnecessary to postulate the mechanism for the formation of thecyclopropanecarboxylic acid esters in which R is OR' from the aryl allylsulfone and the a,B-ethylenic ester, the reaction can be considered totake place in two steps. In the first step, the sulfone function of thecompound of Formula lV activates the methylene and methine group in theaposition thereby inducing the 1,4-addition of the sulfone to theconjugated double bond of the said ester, notwithstanding theunfavorable steric and electron effects of Z and Z After protonation ofthe intermediate adduct, the formation of a compound of Formula Vll wasascertained which may actually exist in the basic and aprotic reactionmedium in the form of an a-carboalkoxylic anion or its enol form. In thesecond step which may occur simultaneously, the sulfone function of theintermediate of Formula Vll or its a-carboalkoxylic or enol anion playsa new role due to its ability to be eliminated in the form of an Arso-sulfinic anion thereby promoting the intramolecular cyclization to formthe cyclopropanecarboxylic acid ester in which R is OR. However, theinvention is not intended to be limited to the above theoreticalconsiderations. Moreover, the invention covers the entire process wherean intermediate of Formula VII or an analog is isolated and then reactedto form the said cyclopropanecarboxylic acid ester.

The hydrolysis of the cyclopropanecarboxylic acid esters wherein R isOR"' to the free acids may be effected with an alkali metal hydroxidesuch as sodium hydroxide or potassium hydroxide and is usually effectedin an aqueous alcohol medium such as methanol, ethanol or glycol.

The conversion of the free cyclopropanecarboxylic acids of Formula 1into the esters where R is OR can be obtained by various methods withreaction of the corresponding alcohol. The alcohol may be directlyreacted with the said acid in the presence of a strong acid catalyst,preferably with azeotrophic distillation of the water of reactionformed.

However, it may be advantageous to first convert the said free acid intoan acid function derivative such as its acid anhydride, a mixed acidanhydride, its acid chloride or a metal salt which can then be reactedwith the appropriate alcohol to obtain the desired ester of Formula I.The acid anhydride can be obtained by reaction of acetic acid anhydrideand the said free acid, for example.

The cyclopropanecarboxylic acid chloride can be formed by reacting thefree acid of Formula I with a chlorinating agent such as thionylchloride, phosphorus trichloride, phosphorus pentachloride, etc.Preferably, the said acid is reacted with thionyl chloride in a benzenemedium to form the acid chloride which is then reacted with theappropriate alcohol in an aromatic hydrocarbon solvent such as benzeneor toluene in the presence of a tertiary amine such as pyridine to bindthe hydrochloric acid formed.

A metal salt of the cyclopropanecarboxylic acid of Formula I can beformed by neutralizing the said acid with an alcohol solution of alkalimetal alcoholate followed by removal of the solvent and the alkali metalsalt of the said acid can then be reacted with a halogenated derivative,preferably the bromine derivative, of the alcohol in dimethylformamideto form the desired ester.

As a modification of the said process, the cyclopropanecarboxylic acidesters where R is OR' may be transesterified with the desired alcohol byheating the reactants in the presence of sodium while continuouslydistilling off the freed lower alcohol. However, it is sometimesadvantageous for purification to saponify the said acid ester to formthe free acid, react the latter to form again a lower alkyl ester suchas with diazomethane to form the methyl ester and subjecting the latterester to trans-esterification with the desired alcohol.

In another modification of the process, where R and R together form acycloalkyl of three to four carbon atoms, a cyclopropyl or cyclobutyltriaryl phosphonium halide may be condensed with dl-trans caronaldehydeacid in a basic medium to form the corresponding cyclopropanecarboxylicacid. The cyclopropyl or cyclobutyl triaryl phosphonium halide ispreferably cyclopropyl or cyclobutyl tri-phenyl phosphonium halide. Thebasic agent used to effect the condensation of the cyclopropyl orcyclobutyl triaryl phosphonium halide with dl-trans caronaldehyde acidis preferably an alkali metal hydride such as sodium or potassiumhydride and the condensation is preferably conducted in a medium ofdimethoxyethane or dimethoxypropane. Other bases such as alkali metalamides and other solvents such as tetrahydrofuran may be used.

The preparation of cyclopropyl triphenyl phosphonium bromide by thermaldecomposition of 3-(2-oxotetrahydrofuranyl) triphenyl phosplioniumbromide is described by H. Hartung (Angew. Chem. Int. Ed. 4, Page 704(1965)). The preparation of cyclobutyl triphenyl phosphonium bromide bycyclization of 4- bromobutyl triphenyl phosphonium bromide is describedby A. Mondom, Ann, 603,1l5 (1957). Other cyclopropyl and cyclobutyltriaryl phosphonium bromide halides can be prepared by similarprocesses. dltrans caronaldehyde acid (or dl-trans 3-formyl-2,2-dimethyl-cyclopropanecarboxylic acid) can be prepared by the methoddescribed by M. Matsui et al. [Agr. Biol. Vol. 27, No.8, pages 554-557(1963)].

The 2-R"-3-methyl-l-oxo-2-cyclopentene-4-ol wherein R" has the abovedefinition, may be prepared by the process described in J.A.C.S., Vol.71 (1949), p. l 517 or modification of this process or by degradation ofnatural products.

Racemic mixtures of the cyclopropanecarboxylic acids of Formula I can beresolved with optically active organic bases such as ephedrine, ifdesired.

The cyclopentenolone esters of Formula I prepared by the process of theinvention as a rule consist of a mixture of diastereoisomers. Forexample, the ester obtained by esterification of a d,l-transcyclopropanecarboxylic acid of Formula I when R is OH withdl-allethrolone may consist of four diastereoisomers forming tworacemates in varying proportions one racemate consists of the ester ofthe -trans acid with -allethrolone and of the ester of the -trans acidwith -allethrolone and the second racemate consists of the. ester of the-trans acid ester with -allethrolone and of the ester of -trans acidwith allethrolone. As another example, the ester obtained by startingwith a dl-trans cyclopropane-carboxylic acid of Formula I and-cinerolone consists of two diastereoisomers the ester of the -transacid with -cinerolone and the ester of the -trans acid with -cinerolone.

A preferred group of compounds of Formula I are those compounds whereinZ and Z are selected from the group consisting of hydrogen; lower alkylof one to seven carbon atoms such as methyl, ethyl, propyl, nbutylphenyl which may be substituted; phenyl lower alkyl lower alkenylnon-conjugated with the cyclopropyl ring; lower alkynyl non-conjugatedwith the cyclopropyl ring cycloalkyl and cyclo-alkenyl of three to sevencarbon atoms such as cyclopentyl, cyclohexyl, cyclohexenyl, etc; andheterocyclic such as furyl; R is selected from the group consisting oflower alkyl which may be substituted such as methyl, ethyl, halo ethyletc.; benzyl which may be substituted on the yl, cyclopentenyl,cyclohexenyl; heterocyclic such as furfuryl; and(5-benzyl-furyl-3)-methyl; R and R are selected from the groupconsisting of lower alkyl, lower alkynyl, lower alkenyl, phenyl loweralkyl, phenyl which may be substituted, cycloalkyl and cycloalkenyl ofthree to seven carbon atoms which may be substituted with lower alkyland/or lower alkoxy and R and R together may form a polycyclic radicalsuch as fluorene or together with the carbon atom to which they areattached may form a cycloalkyl, cycloalkenyl and heterocyclic of threeto seven carbon atoms such as cyclohexenyl, cyclopentadienyl which maybe substituted with lower alkyl and/or lower alkoxy; R is lower alkylsuch as methyl; R is hydrogen or lower alkyl and R, and R together withthe carbon atoms to which they are attached form a cycloalkyl,cycloalkenyl or heterocyclic of three to seven carbon atoms; Y ismethylene and Y is methine.

In the following examples there are described several preferredembodiments to illustrate the invention. However, it should beunderstood that the invention is not intended to be limited to thespecific embodiments.

PREPARATION OF REACTANTS l. Preparation of3-ethyl-1-pentene-3-ol Asolution of 93 gm of 3-pentanone in 100 cc of tetrahydrofuran wereintroduced over one hour into 615 cc of a solution of vinyl magnesiumchloride in tetrahydrofuran titrating 1.78 moles/liter under anatmosphere of nitrogen and at a temperature not above 50C. The mixturewas agitated at room temperature for 15 hours. Thereafter, the reactionmixture was cooled to 0C and 500 cc of water were added under vigorousagitation and at a temperature not exceeding +40C. The organic phase wasseparated by decanting and after the aqueous phase was extracted withether the organic phases were combined and dried over magnesium sulfate.Then the solvents were eliminated and the residue obtained was rectifiedunder atmospheric pressure, to obtain gm of 3-ethyl-l-pentene-3-olhaving a boiling point of UPC-132C and a refractive index n,, 1.4345,which was utilized as such for the preparation of l-bromo-3-ethyl-2-pentene.

Working in the same fashion, but starting with 4-heptanone,-3-propyl-l-hexene-3-ol having a boiling point of 6468C under 14 mm Hgand a refractive index n 1.438 was obtained.

By starting with 2,4-dimethyl-pentane-3-one,3-isopropyl-4-methyl-l-pentene-3-ol having a boiling point of 7l-75 Cunder 30 mm pressure of mercury and a refractive index n 1.443 wasobtained.

By starting with 2,6-dimethyl-4-heptanone,3-iosbutyl-S-methyl-l-hexene3-ol having a boiling point of 87C under 20mm pressure of mercury and a refractive index m, 1.4395 was obtained.This compound is not described in the literature.

By starting with benzophenone, 1,1-diphenyl-2- propene-l-ol having aboiling point of 10S-1 10C under 0.04 mm pressure of mercury and arefractive index n,, 1.593 was obtained. This compound is not describedin the literature.

By starting with 4,4-dimethyl-cyclohexane-1one, 1-vinyl-4,4-dimethyl-cyclohexane-l-ol having a boiling point of 93-96 Cunder mm pressure of mercury was obtained. This compound is notdescribed in the literature.

By starting with 3,3,5,5-tetramethyl-cyclohexane-1- one,3,3,5,5-tetramethy1-1-vinyl-cyc1ohexane-1-ol having a boiling point of98C under 18 mm pressure of mercury and a refractive index n,, 1.467 wasobtained.

By starting with 2,3,5,6-tetrahydropyrane-4-one,2,3,5,6-tetrahydro-4-vinyl-pyrane-4-ol having a boiling point of 97100Cunder 21 mm pressure of mercury and a refractive index m, 1.473 wasobtained. This compound is not described in the literature.

By starting with cyclobutanone, l-vinyl-cyclobutanel-ol having a boilingpoint of 4650C. under 17 mm pressure of mercury and a refractive indexn,, 1.4590 was obtained. This compound is not described in theliterature.

11. Preparation of 1-bromo-3-ethy1-2-pentene A solution of 19.1 cc ofphosphorus tribromide in 125 cc of petroleum ether (boiling point of50-70C) was introduced within 1 hour and at a temperature of about -20Cinto a mixture of 64 gm of 3-ethy1-1-pentene-3-ol and 190 cc ofpetroleum ether (boiling point 5070C). The reaction mixture was agitatedfor 1 hour and minutes at 10C and then it was poured into a mixture ofsalt water and ice. The organic phase was decanted, washed first with anaqueous sodium bicarbonate solution and then with an aqueous sodiumchloride solution. The combined aqueous phases were re-extracted withpetroleum ether and the re-extractions were combined with the principalorganic solution. The solution thus obtained was dried over magnesiumsulfate, filtered and dried. The solvent was removed under normalpressure in the presence of potassium carbonate in an inert atmospherein an apparatus provided with a rectifying column. The resultant residuewas then rectified under reduced pressure in the presence of potassiumcarbonate and in an inert atmosphere to obtain 87.175 gm of 1-bromo-3-ethyl-Z-pentene having a boiling point of 74C under 28 mm pressure ofmercury. This product was utilized as such for the next step. It wasmaintained in an inert atmosphere in the presence of potassiumcarbonate. Working in the same fashion, but starting with 3-propy1-1-hexene-3-ol, 1-bromo-3-propyl-2-hexene having a boiling pointof 85-90C under 17 mm pressure of mercury and a refractive index n 1.483was obtained.

By starting with 3-isopropyl-4-methyl-l-pentene-3- ol,1-bromo-3-isopropyl-4-methyl-2-pentene having a boiling point of 92Cunder 32 mm pressure of mercury and a refractive index n 1.479 wasobtained. This compound is not described in the literature.

By starting with 3-isobutyl-5-methy1-1-hexene-3-ol,1-bromo-3-isobutyl-5-methy1-2-hexene with a boiling point of 70-76Cunder 1 mm pressure of mercury and a refractive index n 1.4750 wasobtained.

This compound is not described in the literature.

By starting with 2,6-dimethyl-1-vinyl-cyclohexane-1- ol,1-bromo-2-(2,6-dimethylcyclohexylidene)-ethane having a boiling point of115120 C under 20 mm pressure of mercury was obtained. This compound isnot described in the literature.

By starting with 1-vinyl-4,4-dimethylcyclohexane-1- ol,l-bromo-2-(4,4'-dimethylcyclohexylidene)-ethane having a refractiveindex n 1.5060 was obtained. This compound is not described in theliterature.

By starting with 3,3,5,5-tetramethyl-1-viny1-cyclohexane-l-ol,1-bromo-2-(3',3,5',5'-tetramethylcyclohexylidene)-ethane having aboiling point of 87C under 0.5 mm pressure of mercury and a refractiveindex 12 1.505 was obtained.

By starting with 2,3,5,6-tetrahydro-4-viny1-pyran-4- o1,1-bromo-2-(2',3,5',6'-tetrahydro-4'-pyranylidene)-ethane having aboiling point of 73C under 1.5 mm pressure of mercury and a refractiveindex n 1.529 was obtained. This compound is not described in theliterature.

By starting with 1-vinyl-cyclobutane-1'0l, l-bromo-2-cyclobuty1idene-ethane with a boiling point of 5658C under 15 mmpressure of mercury and a refractive index r1 1.5160 was obtained. Thiscompound is not described in the literature.

By starting with 1,1-diphenyl-2propene-1-ol, 1-br0mo-3,B-diphenyl-Z-propene having a melting point of 43C was obtained.This compound is not described in the literature.

111. Preparation of 3-methyl-2-cyclohexene-1-ol 8.25 gm of lithiumaluminum hydride were introduced under an atmosphere of nitrogen into ccof tetrahydrofuran and at a temperature of 0C a solution of 33 gm of3-methyl-2-cyclohexene-l-one obtained according to the method describedby KLAZE/Ann.281,94(), in 35 cc of tetrahydrofuran were added theretowithin the space of about 45 minutes. The reaction mixture was agitatedat room temperature for 1 hour. The excess hydride was decomposed byaddition of ethyl ether saturated with water and then by addition ofwater. The precipitate thus formed was eliminated by filtration and thefiltrate obtained was dried over magnesium sulfate and concentrated todryness to obtain 31.85 gm of raw 3- methyl-2-cyclohexene-1-ol whichproduct was utilized as such for the next step. This product was aliquid with a refractive index of n,, 1.4785.

EXAMPLE 1 Preparation of dl-trans 3,3-dimethyl-2-(2-ethyl-l'- butenyl)cyclopropanecarboxylic acid and its ester with dl-allethrolone Step A:Preparation of (3-ethyl-2-pentenyl)-phenylsulfone 1.85 gm of sodiumcarbonate and 18.5 gm of sodium phenyl sulfinate were introduced into 60cc of methanol. Then 20 gm of 1-bromo-3-ethyl-2-pentene were addedwithin the space of about 30 minutes at room temperature to theresulting suspension, which then was agitated for 1 hour and 30 minutesat room temperature. Then the reaction mixture was poured into ice-waterand the organic phase was was separated by decanting. The aqueous phasewas extracted with ethyl ether and the ether extractswere combined withthe principal organic solution. The solution thus obtained was driedover magnesium sulfate and the solvent was removed under reducedpressure to obtain 21.665 gm of (3-ethyl-2-pentenyl)-phenylsulfone. Asample of this product was rectified under reduced pressure and theboiling point was 125C under 0.02 mm pressure of mercury and itsrefractive index n 1.530.

Analysis: C H SO molecular weight 238.34 Calculated: C:65.53% l-l:7.61%S: 13.46% Found: C:65.4% H:7.6% S:l 3.2%

This compound is not described in the literature. Step B: Preparation ofethyl dl-trans 3,3-dimethyl-z-( 2 '-ethyl-l -butenyl)-cyclopropanecarboxylate Thirty-nine gm of potassium tert.-butylatetitering 87 percent were dissolved in 240 cc of dimethylformamide andafter 30 gm of (3-ethyl-2-pentenyl)-phenyl sulfone were introduced intothis solution, it was then agitated for 15 minutes. Next, 29.1 gm ofethyl B, B- dimethylacrylate were introduced dropwise into the reactionmixture within the space of 10 minutes. This mixture was then agitatedfor 2 hours at room temperature, cooled thereafter to C, and poured intoa mixture of ice and a dilute aqueous solution of hydrochloric acid.Then the reaction mixture was extracted with ethyl ether and the ethersolutions were combined,

washed first with an aqueous solution of sodium chloride, then with anaqueous solution of sodium bicarbonate and finally again with an aqueoussolution of sodium chloride. The ether solution was dried over magnesiumsulfate, concentrated to dryness under reduced pressure and thenrectified under reduced pressure to obtain 25.57 gm of raw ethyldl-trans 3,3- dimethyl-2-(2'-ethyl-1'-butenyl)-cyclopropanecarboxylatehaving a boiling point of 70C72C under 0.08 mm pressure of mercury and arefractive index u 1.462. This product was utilized as such for the nextstep.

This product is not described in the literature. Step C: Preparation ofdl-trans-3,3-dimethyl-2-(2- ethyl 1-butenyl)'-cyclopropanecarboxylicacid Twenty gm of raw ethyl dl-trans 3,3-dimethyl-2-(2-ethyl-l'-butenyl)-cyclopropanecarboxylate were introduced into a mixtureof 100 cc of a 2N methanolic sodium hydroxide solution and 20 cc ofwater. The reaction mixture was heated to reflux which was maintainedfor 1 hour. Then the methanol was eliminated under reduced pressure andthe remainder was diluted with water. The aqueous phase was extractedwith ethyl ether and the ether extracts were combined. The ethersolution thus obtained was washed once with water. The aqueous washwaters were combined with the principal aqueous phase, and all of theaqueous phases combined were acidified with a dilute aqueous solution ofhydrochloric acid. The acidified aqueous phase was extracted withmethylene chloride and the methylene chloride solution was washed withwater, dried over magnesium sulfate and concentrated to dryness underreduced pressure. The residual oil was rectified under reduced pressureto obtain 11.95 gm of dl-trans 3,3- dimethyl-2-( 2'-ethyl-l'-butenyl)-cyclopropane-carboxylic acid having a boiling point of 1 Cunder 0.05 mm of mercury pressure and melting point 363 7C. A sample ofthis product, purified by rectification under reduced pressure, had aboiling point 94C under 0.01 mm pressure of mercury and a melting point37C.

Analysis: C l'l O molecular weight= 196.28 Calculated: C: 73.42% H:10.27%

Found: C: 73.5% H: 10.0

This product is not described in the literature.

Step D: Preparation of dl-trans 3,3-dimethyl-2-(2'- ethyl-1'-butenyl)-cyclopropanecarboxylic acid chloride.

Five gm of dl-trans3,3-dimethyl-2-(2-ethyl-1-butenyl)-cyclopropanecarboxylic acid wereintroduced into 10 cc of petroleum ether (boiling point 5070 C) andafter 2.8 cc of thionyl chloride were added, the mixture was agitated atroom temperature for 1 hour and 30 minutes. The petroleum ether andexcess thionyl chloride were eliminated by distillation and the residuewas rectified under reduced pressure to obtain 5.25 gm of dl-trans3,3-dimethyl-2-(2'-ethyl-1'-butenyl)-cyclopropanecarboxylic acidchloride having a boiling point of 68C under 0.2 mm pressure of mercury.This product was utilized as such for the next step.

This product is not described in the literature.

Step E: Preparation of dl-trans 3,3-dimethyl-2-(2-ethyl-l'-butenyl)-cyclopropanecarboxylate of dl-allethrolone 5.24 gm ofdl-trans 3,3-dimethyl-2-(2'-ethyl-l -butenyl)-cyclopropanecarboxylicacid chloride were introduced into a mixture of 30 cc of benzene and .6cc of pyridine. Then a solution of 3.7 gm of dl-allethrolone in 5 ccof'benzene was added over about 10 minutes and at a temperature of 0C.The reaction mixture was agitated for about 15 hours at roomtemperature, after which the pyridine hydrochloride formed waseliminated by filtration. The organic phase was washed first with adilute aqueous hydrochloric acid solution, then with water, next with anaqueous sodium bicarbonate solution and finally again with water. Thesolution thus obtained was dried over magnesium sulfate and thenconcentrated to dryness under reduced pressure. The'recovered residuewas subjected to chromatography through alumina with elution withcyclohexane to obtain 5.445 gm of dl-trans 3,3- dimethyl-2-(2'-ethyl-1-butenyl)-cyclopropane-carboxylate of dl-allethrolone having arefractive index of n,,"= 1.4520. Analysis: C H O molecular weight 330.45 Calculated: C: 76.32% H: 9.15% Found: C: 76.1% H: 9.0%

This product is not described in the literature.

EXAMPLE 11 Preparation of dl-trans 3,3-dimethyl-2-(2-isobutyl-4'-methyl-l'-pentenyl)-cyclopropanecarboxylic acid and its ester withdl-allethrolone Step A: Preparation of (3-isobutyl-5-methyl-2-hexenyl)-phenyl-sulfone Fifty-five gm of sodium phenyl sulfinate weredissolved in 500 cc of methanol and then 8 gm of potassium carbonate, 1gm of sodium iodide and finally 7] gm of1-bromo-3-isobutyl-5-methyl-2-hexene were added to the solution, whichwas then agitated for 15 hours at room temperature. Thereafter, thereaction mixture was concentrated to dryness under reduced pressure andwater was added thereto. The aqueous phase was extracted with methylenechloride and the methylene chloride extracts were combined. The organicsolution thus obtained was washed with water, dried and concentrated todryness under reduced pressure. The residue was subjected tochromatography through an alumina column to obtain 62.32 gm of the(3-isobutyl- 5-methyl-2-hexenyl)phenylsulfone. This product is notdescribed in the literature.

Step B: Preparation of methyl dl-trans 3,3dimethyl-2-(2-isobutyl-4'-methyl-1-pentenyl)-cycl0propanc-carboxylate 24.56 gm ofpotassium tert-butylate titering 87 percent were dissolved in 120 cc ofdimethylformamide and 28 gm of (3-isobutyl-5-methyl-2-hexenyl) phenylsulfone were added. The solution was agitated for 2 minutes and then 18cc of methyl B, B-dimethylacrylate were introduced therein within aboutminutes. The reaction mixture was agitated for 2 hours at roomtemperature, then poured into a mixture of a dilute aqueous hydrochloricacid solution and water. The aqueous phase was extracted with methylenechloride and the methylene chloride extracts were combined and wassuccessively washed with water, with an aqueous solution of sodiumbicarbonate and again with water, then dried and concentrated todryness. The resultant residue was rectified under reduced pressure toobtain 24.68 gm of the desired methyl dl-trans 3,3-dimethyl-2-(2'-isobutyl-4-methyl-1'-pentenyl)-cyclopropanecarboxylate, having aboiling point of l 13 C under 1 mm pressure of mercury.

This product is not described in the literature.

Step C: Preparation of dl-trans 3,3-dimethyl-2-(2'- isobutyl-4'-methyl-1-pentenyl)-cyc1opropanecarboxylic acid.

Eighteen cc of a 10 N aqueous sodium hydroxide solution ere introducedinto a mixture of 100 cc of methanol and 10 cc of water. The solutionwas then brought to reflux under a current of nitrogen and reflux wasmaintained for 10 minutes after which a solution of 24.6 gm of methyldl-trans 3,3-dimethyl-2-(2'-isobutyl-4'-methyl-1-pentenyl)-cyclopropanecarboxylate in 30 cc of methanol wasadded. The reaction mixture was agitated for 1 hour at reflux afterwhich water was added and the methanol was eliminated. Then the reactionmixture was cooled and the aqueous phase was extracted with ethyl ether.The ether extracts were combined and washed with water. The wash waterswere Step D: Preparation of dl-trans 3,3-dimethyl-2-(2'- isobutyl-4'-methyl-1-pentenyl)-cyclopropanecarboxylic acid chloride.

Eight gm of dl-trans 3,3-dimethyl-2-(2-isobutyl-4'-methyl-l-pentenyl)-cyclopropane carboxylic acid were dissolved under anatmosphere of nitrogen in 25 cc of petroleum ether (boiling point -70C)and then, 3.5 cc of thionyl chloride were slowly added. The solution wasagitated first for 1 hour and 30 minutes at room temperature, then for30 minutes at 40C. The reaction solution was concentrated to drynessunder reduced pressure and then rectified to obtain 7.4 gm of thedesired dl-trans 3,3-dimethyl-2-(2'-isobutyl-4-methyl-1-pentenyl)-cyclopropanecarboxylic acid chloride having a boilingpoint of l 18C under 1.5 mm pressure of mercury and a refractive indexr1 1.4775. The product was utilized as such for the next step.

This product is not described in the literature.

Step E: Preparation of dl-trans 3,3-dimethyl-2-(2'- isobutyl-4'-methyl-l'-pentenyl)-cyclopropane-carboxylate of dl-allethrolone Under anatmosphere of nitrogen, 7.335 gm of dltrans3,3-dimethy1-2-(2'-isobutyl-4'-methyl-1'-pentenyl)-cyclopropane-carb0xylicacid chloride were introduced into 20 cc of benzene and after a solutionof 4 gm of dl-allethrolone in a mixture of 8 cc of pyridine and 20 cc ofbenzene was added at 10C, the reaction solution was agitated for 15hours at room temperature. Thereafter, first 1 cc of formic acid andthen water was added. The aqueous phase was extracted with ethyl etherand the ether extracts were combined; successively washed with a diluteaqueous solution of hydrochloric acid, with an aqueous solution ofsodium bicarbonate and finally with water, and then dried andconcentrated to dryness.

The resultant residue was dissolved in benzene and the benzene solutionwas passed through an alumina column, then it was again concentrated todryness. The residue was rectified under reduced pressure to obtain 4.9gm of the desired-dl-trans 3,3-dimethyl-2-(2'-isobutyl-4'-methyl-l'-pentenyl)-cyclopropanecarboxylate of 5 dl-allethrolone having aboiling point of 160C under 0.07 mm pressure of mercury and a refractiveindex n 1.4950.

Analysis: C H O molecular weight 386.55 Calculated: C: 77.67% H: 9.91%

combined with the principal aqueous phase and the Found.C:77 9% "297%other solution containing the neutral fraction was eliminated.

The combined aqueous phases were acidified with a I dilute aqueoushydrochloric acid solution and the acid aqueous phase was extracted withether. The ether ex- Ultra-violet Spectra (in ethanol) A max. 225 mu (620,300)

This product is not described in the literature.

EXAMPLE lll Preparation of dl-trans3,3-dimethyl-2-(2',2-diphenyl-vinyl)-cyclopropanecarboxylic acid and itsester with dl-allethrolone Step A: Preparation of(3,3-diphenyl-2-propenyl)- methyl-l'-pentenyl)cyclopropanecarboxylicacid having a melting point of 74C. Analysis: C, H O molecularweight=252.38

Calculated: C: 76.14% H: 11.18%

Found: C: 76.1% H: 10.9%

This product is not described in the literature.

phenyl-sulfone 15.5 gm of sodium phenyl sulfinate and 1.5 gm of sodiumcarbonate were introduced into cc of methanol. Then 25.6 gm ofl-brom0-3,3-diphenyl-2- 5 propene were added to the reaction mixtureunder an atmosphere of nitrogen and at room temperature which was thenagitated for 1 hour and 30 minutes. Next, the

reaction mixture was poured into cold water and extracted with methylenechloride. The methylene chloride extracts were combined, washed withwater, dried and concentrated to dryness. The residue was partlycrystallized. The precipitate formed was isolated by vacuum filteringand dried to obtain 25.48 gm of (3,3-diphenyl-2-propenyl)-pheny1 sulfonehaving a melting point of 104C. A sample of this product, recrystallizedfrom isopropyl ether, had a melting point of 106C. Analysis: C ,H SOmolecular weight 334.43 Calculated: C: 75.41% H: 5.42% S: 9.58% Found:C: 75.3% H: 5.4% S: 9.4%

This product is not described in the literature. Step B: Preparation ofethyl dl-trans 3,3-dimethyl-2-(2',2'-diphenylvinyl)-cyclopropanecarboxylate Under an atmosphere ofnitrogen, 21.6 gm of potassium tert. butylate titering 87 percent and28.08 gm of (3,3-diphenyl-2-propenyl) phenyl sulfone were introducedinto 150 cc of dimethylsulfoxide and the mixture was agitated for 30minutes at 105C. Then 17.5 cc of ethyl B, B-dimethyl-acrylate were addedand the reaction mixture was agitated for 2 hours, followed by additionof 17.5 cc more of ethyl B, B-dimethyl-acrylate and the mixture wasagitated for 7 hours at 105C. Thereafter the reaction mixture was cooledto C and acidified with a dilute aqueous solution of hydrochloric acid.The aqueous phase was extracted with methylene chloride and themethylene chloride extracts were combined; washed first with an aqueoussolution of sodium bicarbonate, then with water, then dried andconcentrated to dryness. The partly crystallized residue was filtered toeliminate any impurity. The filtrate was subjected to chromatographythrough alumina with elution with cyclohexane to obtain the desiredethyl dltrans 3,3-dimethyl-2-(2', 2' -diphenylvinyl)-cyclopropanecarboxylate which was used as such for the next step.

This product is not described in the literature. Step C: Preparation ofdl-trans 3,3-dimethyl-2-(2',2'- diphenylvinyl)-cyclopropanecarboxylicacid 42.7 cc of a 2N methanolic sodium hydroxide solution wereintroduced into 100 cc of methanol and 10 cc of water, followed by 18.45gm of ethyl dl-trans 3,3-dimethyl-2-(2',2'-diphenylvinyl)-cyc1opropanecarboxylate were addedthereto. The mixture was brought to reflux and maintained there for 1hour and 30 minutes. The methanol was removed by distillation and waterwas added. Next the aqueous phase was extracted with ethyl ether toeliminate the neutral fraction and the combined ether extracts werewashed with water and the wash water was combined with the principalaqueous phase. Then the entire aqueous phase was acidified with a diluteaqueous solution of hydrochloric acid which was then repeatedlyextracted with methylene chloride; the methylene chloride solutions werecombined, washed with water dried and concentrated to dryness to obtain7.95 gm of dl-trans 3,3-dimethyl-2-(2',2'-diphenyl-vinyl)-cyclopropanecarboxylic acid having a melting pointof l C. A sample of this product crystallized, from a mixture ofisopropyl ether and petroleum ether, .had a melting point of 1 15 C.

Analysis: c n o molecular weight= 292.36 Calculated: C: 82.15% H: 6.89%Found: C: 82.1% H: 7.0%

According to its N.M.R. spectra, this product consisted of the transderivative containing about 10 percent of the cis derivative. Thisproduct is not described in the literature.

Step D: Preparation of dl-trans 3,3-dimethyl-2-(2',2-diphenylvinyl)-cyclopropanecarboxylic acid chloride 2.5 gm of dl-trans3,3-dimethyl2-(2,2'-diphenyl-vinyl)-cyclopropanecarboxylic acid wereintroduced into 10 cc of benzene and after the addition of 0.9 cc ofthionyl chloride, the mixture was maintained at room temperature for 20minutes, then heated to C and maintained at this temperature for 3hours. Excess benzene and thionyl chloride were eliminated bydistillation under vacuum. The raw-dl-trans 3,3-dimethyl-2-(2,2-diphenylvinyl)-cyclopropanecarboxylic acid chloride thus obtainedin a quantitative yield was utilized as such for the next step.

This product is not described in the literature. Step E: Preparation ofdl-trans 3,3-dimethyl-2-(2,2'- diphenylvinyl)-cyclopropanecarboxylate ofdl-allethrolone The raw dl-trans3,3-dimethyl-2-(2',2'-diphenylvinyl)-cyclopropanecarboxylic acidchloride (corresponding to 2.5 gm of acid) was introduced into 13 cc ofbenzene and 1.2 cc of pyridine and 1.3 gm of dlallethrolone were addedthereto. The reaction mixture was agitated for about 15 hours at roomtemperature. The precipitate formed was eliminated by filtration and thebenzene filtrate was washed first with a dilute aqueous solution ofhydrochloric acid, then with water, then with an aqueous solution ofsodium bicarbonate and lastly again with water. Next the benzenesolution was dried and concentrated to dryness. The residue wassubjected to chromatography through alumina with elution with benzene toobtain 2.034 gm of dl-trans 3,3- dimethyl-2-( 2 ,2-diphenylvinyl)-cyclopropanecarboxylate of dl-allethrolone having arefractive index m, 1.569.

Analysis: C H O molecular weight 426.53 Calculated: C: 81.66% H: 7.09%

Found: C: 81.9% H: 7.2%

Ultra-Violet Spectra (in ethanol) max.: 227 mp. (e 28,100)

A max.: 262 mp. (e= 17,050)

This product is not described in the literature.

EXAMPLE lV Preparation of dl-trans3,3-dimethyl-2-cyclopentylidene-methyl-cyclopropanecarboxylic acid andits,-

ester with dl-allethrolone Step A: Preparation of(2-cyclopentylidene-ethyl)- phenyl sulfone 22.3 gm of sodium phenylsulfinate', 2.2 gm of potassium carbonate and 0.2 gm of sodium iodidewere introduced into 50 cc of methanol. Then 23.6 gm of 1-bromo-2-cyclopentylidene-ethane were added at a temperature of about+10C and under agitation and the reaction mixture was agitated for 2hours at 20C. Thereafter, the reaction mixture was poured into ice waterand cooled to 0C. The precipitate formed was isolated by vacuumfiltering and dried under vacuum in the presence of potassium hydroxideto obtain 15 gm of (Z-cyclopentylidene-ethyl)-phenyl sulfone having amelting point of 68C. A sample of the product crystallized fromisopropyl ether had a melting point of 68C.

Analysis: C H SO molecular weight 236.33 calculated: C: 66.06% H: 6.82%S: 13.57% Found: C: 65.8% H: 6.8% S: 13.2%

This product is not described in the literature.

The l-bromo 2-cyclopentylidene-ethane was prepared according to theprocess described in Bull. Soc. Chim. 1964, pg, 2618.

Step B: Preparation of ethyl dl-trans 3,3-dimcthyl-2-cyclopentylidene-methyl-cyclopropanecarboxylate Under an atmosphere ofnitrogen, first 16.5 gm of potassium ter-butylate titering 87 percent,then 15 gm of (Z-cycIopentyIidenc-ethyl)phenyl sulfone were introducedinto 100 cc of dimethylformamide. The mixture was agitated for 10minutes and then 16 cc of ethyl Bfi-dimethyl-acrylate were added overabout 10 minutes and the reaction mixture was agitated for 3 hours.Thereafter, the reaction mixture was cooled to C and poured into adilute aqueous solution of hydrochloric acid. The aqueous phase wasextracted with methylene chloride, the methylene chloride extracts werecombined, washed first with a dilute aqueous solution of sodiumbicarbonate, then with water, then dried and concentrated to drynessunder reduced pressure. The resultant residue was rectified underreduced pressure to obtain 12.28 gm of raw ethyl dltrans3,3-dimethyl-2-cyclopentylidene-methylcyclopropanecarboxylate having aboiling point of 88C under 0.05 mm pressure of mercury, and it wasutilized as such for the following step.

This product is not described in the literature.

Step C: Preparation of dl-trans 3,3-dimethyl-2-cyclopentylidene-methyl-cyclopropanecarboxylic acid Under an atmosphereof nitrogen, 12.28 gm of raw ethyl dl-trans3,3-dimethyl-2-cyclopentylidene-methylcyclopropanecarboxylate wereintroduced into a mixture consisting of 32 cc of a 2 N methanolic sodiumhydroxide solution, 5 cc of water and 5 cc of methanol. The reactionmixture was refluxed for 1 hour and 30 minutes, then cooled to roomtemperature and a waterice mixture was added. Next, the aqueous phasewas extracted with ethyl ether to eliminate the neutral fractions andthe combined ether extracts were washed with water. The aqueous washwaters were combined with the principal aqueous phase which was thenacidified with a dilute aqueous solution of hydrochloric acid. Then theacidified aqueous phase was extracted with methylene chloride and themethylene chloride extracts were combined, washed with water, dried andconcentrated to dryness under reduced pressure. The residue wasrectified under vacuum to obtain 5.27 gm of dl-trans 3,3-dimethyl-2-cyclopentylidene-methylcyclopropanecarboxylic acid having a boilingpoint of l 15C under 0.1 mm pressure of mercury and a melting point of59C.

Analysis: C H O molecular weight 194.26 Calculated: C: 74.19% H: 9.34%

Found: C: 74.1% H: 9.3%

This product is not described in the literature.

Step D: Preparation of dl-trans 3,3-dimethyl-2-cyclopentylidene-methyl-cyclopropanecarboxylic acid I chloride Under anatmosphere of nitrogen, 2.5 gm of dl-trans3,3-dimethyl-2-cyclopentylidene-methylcyclopropanecarboxylic acid wereintroduced into cc of benzene and 1.04 cc of thionyl chloride were addedwithin about 30 minutes and under agitation and the reaction mixture wasagitated for l hour at room rectified under reduced pressure to obtain2.2 gm of raw dl-trans3,3-dimethyl-2-cyclopentylidene-methylcyclopropanecarboxylic acidchloride having a boiling point of 82C under 0.25 mm pressure of mercuryand it was utilized as such for the next step.

This product is not described in the literature. Step E: Preparation ofdl-trans 3,3-dimethyl-2- cyclopentylidene-methyl-cyclopropanccarboxylatcof dlallcthrolone Under an atmosphere of nitrogen, 2.2 gm of dl-trans3,3-dimethyl-2-cyclopentylidene-methylcyclopropane-carboxylic acidchloride and 2 cc of pyridine were introduced into 15 cc of anhydrousbenzene. 1.75 gm of dl-allethrolone dissolved in 5 cc of benzene wereadded over about 10 minutes and the mixture was agitated for about 15hours at room temperature. The precipitate formed was eliminated byfiltration and the benzene filtrate was washed first with salt water,then with a dilute aqueous solution of hydrochloric acid and again withsalt water. The aqueous phases were extracted with ether and the etherextracts were combined with the benzene solution. The organic solutionthus obtained was dried and concentrated to dryness. The residue wassubjected to chromatography through an alumina column with elution withbenzene and methylene chloride obtain 3.015 gm of dl-trans3,3-dirnethyl-2-cyclopentylidene-methylcyclopropanecarboxylate ofdl-allethrolone having a refractive index u 1.5195. Ultraviolet Spectra(in ethanol) A max.: 225-226 mp. (e= 20,700) Analysis: C ,H O molecularweight 328.43

Calculated: C: 76.79% H: 8.59% 'Found: C: 76.6% H: 8.4%

This product is not described in the literature.

EXAMPLE V Preparation of dl-trans3,3-dimethyl-2-cyclohexylidene-methyl-cyclopropanecarboxylic acid andits ester with dl-allethrolone Step A: Preparation of(2-cyclohexylidene-ethyl)- phenyl sulfone First, 38.5 gm of sodiumphenyl sulfinate and then 3.85 gm of sodium carbonate were introducedinto 116 cc of methanol and 44 gm of freshly prepared l-bromo-2-cyclohexylidene-ethane were added dropwise over 30 minutes and at roomtemperature. The reaction mixture was then agitated for 1 hour and 30minutes at room temperature after which the reaction mixture was pouredinto 400 cc of ice water. The precipitate formed was vacuum filtered,washed with water and dried. The raw product thus obtained was dissolvedat high temperature in a mixture consisting of methylene chloride andmethanol. The solution obtained was dried over magnesium sulfate,concentrated to a small volume and admixed with isopropyl ether. Theprecipitate formed was vacuum filtered and dried to obtain 36.4 gm of (2cyclohexylidene-ethyl)-phenyl sulfone, having a melting point of C. Asample of this product, crystallized from isopropyl ether, had a meltingpoint of 70C. Analysis: C H SO molecular weight 250.35 Calculated: C:67.16% H: 7.24% S: 12.81

Found: C: 67% H: 7.1% S: 12.5%

This product is not described in the literature.

The l-bromo-2-cyclohexylideneethane was prepared according to theprocess described in Helvotica 1942), vol. 25, pg. 29.

Step B: Preparation of ethyl dl-trans 3,3-dimethy1-2-cyclohexylidene-methyl-cyclopropanecarboxylate 20.6 gm of potassiumtert.-butylate titering 87 percent were introduced into 120 cc ofdimethylformamide and then 20 gm of (2-cyclohexylidene-ethyl)-pheny1sulfone were added thereto. After 10 minutes, 17.3 cc of ethylB,B-dimethylacylate were added and the mixture was agitated for 1 hourat room temperature. Thereafter, the reaction mixture was cooled toabout +5C, acidified with a dilute aqueous solution of hydrochloric acidand the aqueous phase was extracted with methylene chloride.

The methylene chloride solution obtained was washed first with anaqueous solution of sodium bicarbonate, then with water, dried overmagnesium sulfate and concentrated to dryness under reduced pressure toobtain 22.75 gm of ethyl dl-trans 3,3-dimethy1-2-cyclohexylidene-methyl-cyclopropanecarboxylate which was utilized assuch for the next step.

This product is not described in the literature.

Step C: Preparation of dl-trans 3,3-dimethyl-2-cyclohexylidene-methyl-cyclopropanecarboxylic acid 22.75 gm of ethyldl-trans 3,3-dimethyl-2-cyc1ohexylidene-methyl-cyclopropanecarboxylatewere introduced into a mixture consisting of 70 cc of a 2N methanolicsodium hydroxide solution, 2.5 cc of water and 25 cc of methanol. Thereaction mixture was heated to reflux and maintained at reflux for 45minutes. Thereafter, the methanol was removed under reduced pressure andwater was added to the residue. The insoluble matter formed (the sodiumsalt of the desired acid) was vacuum filtered, then washed first withwater, then withether, and these wash-waters were eliminated. The saidproduct was agitated with 100 cc of a dilute aqueous solution ofhydrochloric acid and 100 cc of methylene chloride until totaldissolution had been attained. The organic phase was then separated bydecanting and it was washed with water. The wash waters were extractedwith methylene chloride. The said methylene chloride extracts werecombined with the principal methylene chloride solution, dried overmagnesium sulfate and finally concentrated to dryness under reducedpressure. The residue thus obtained was admixed with petroleum ether andthe precipitate formed was vacuum filtered, washed with petroleum etherand dried to obtain the desired d1- trans3,3-dimethyl-2-cyclohexylidene-methy1- cyclopropane carboxylic acid,having a melting point of 88-89C.

Analysis: C H O molecular weight 208.29 Calculated: C: 74.96% H: 9.67%Found: C: 75.1% H: 9.4%

This product is not described in the literature.

Step D: Preparation of dl-trans 3,3-dimethyl-2-cyclohexylidene-methyl-cyclopropanecarboxylic acid chloride.

Three gm of dl-trans3,3-dimethyl-2-cyclohexylidene-methyl-cyclopropanecarboxylic acid wereintroduced into 15 cc of petroleum ether (boiling point 5070C) and then1.55 cc of thionyl chloride were added over about 30 minutes, and themixture was agitated at room temperature for about 1 hour. Thereafter,the petroleum ether was eliminated undercyclohexylidene-methyl-cyclopropanecarboxylate reduced pressure and theraw acid chloride was rectified under reduced pressure to obtain 2.66 gmof the desired dl-trans3,3-dimethyl-Z-cyclohexylidenemethyl-cyclopropanecarboxylic acidchloride having a boiling point of 88-90C under 0.35 mm pressure ofmercury and was utilized as such for the next step. This productoccurred in liquid form at room temperature.

This compound is not described in the literature. Step B: Preparation ofdlrtrans 3,3-dimethyl-2- of dl-allethrolone 1.56 gm of dl-trans3,3-dimethyl-l-cyclohexylidene methyl-cyclopropanecarboxylic acidchloride were introduced into a mixture of 15 cc of benzene and 1.9 ccor pyridine. Then a solution of 1.050 gm of dl-allethrolone in 5 cc ofbenzene was added dropwise within a few minutes and the mixture wasagitated for about 15 hours at room temperature. Thereafter, the

20 precipitate formed was vacuum filtered and the resultant filtrate waswashed successively with a dilute aqueous solution of hydrochloric acid,with an aqueous solution of sodium chloride, with an aqueous solution ofsodium bicarbonate and finally again with an aqueous solution of sodiumchloride. The aqueous wash waters were combined and extracted withbenzene. The benzene extract was combined with the principal benzenesolution and the entire benzene solution was then dried over magnesiumsulfate and concentrated to dryness under reduced pressure. Therecovered residue was purified by chromatography through alumina withelution with cyclohexane to obtain 1.500 gm of dl-trans3,3-dimethyl-2cyclohexylidene-methylcyclopropanecarboxylate ofdl-allethrolone having a refractive index n 1.515. Analysis: C H Omolecular weight=342.46 Calculated: C: 77.15%; H: 8.82% Found: C: 77.4%;H: 9.0%

Ultraviolet Spectra (in ethanol) Amax; 223mg (e= 19,500)

This product is not described in the literature.

EXAMPLE V1 PREPARATION OF dl-trans 3,3-dimethyl-2-(2'- propyl l-penteny1)-cyclopropanecarboxylic acid and its dl-allethrolone esterUsing the procedure of Example 1, l-bromo-3- propyl-2-hexene was reactedwith sodium phenyl sulfinate to form (3-propyl-2-hexenyl)-phenyl sulfonewhich was then reacted with ethyl B,B-dimethyl-acrylate to form ethyldl-trans 3,3-dimethyl2 (2'-propyl-1 -penteny1)-cyclopropanecarboxylatehaving a boiling point of 80C at 0.06 mm Hg and a refractive index1.464. The said ethyl ester was hydrolyzed under alkaline conditions toform dl-trans 3,3-dimethyl-2-(2'- propyl-l '-pentenyl)-cyclopropanecarboxylic acid having a boiling point of 116C at 0.05 mm Hg and arefractive index n 1.4755 which was then reacted with thionyl chlorideto obtain dl-trans 3,3-dimethyl-2-(2'-propyl-l'-pentenyl)-cyclopropanecarboxylic acid chloride having aboiling point of C at 0.04 mm Hg and a refractive index u 1.4795.

The said acid chloride was then reacted with dl-allethrolone to formdl-trans 3,3-dimethyl-2-(2'-propyl 1 '-pentenyl)-cyclopropanecarboxylateof dl-allethrolone having a refractive index 1.499.

EXAMPLE VII PREPARATION of dl-trans 3,3-dimethyl-2-(2'- isopropyl-3'-methyl-1 -butenyl)-cyclopropanecarboxylic acid and its dl-allethroloneester Using the procedure of Example I, l-bromo-3-isopropyl-4-methyl-2-pentene was reacted with sodium phenyl sulfinate toform (3-isopropyl-4-methyl-2-pentenyl)-phenyl sulfone having a meltingpoint of 50C which was then reacted with ethyl B,B-dimethylacrylate toform ethyl dl-trans 3,3-dimethyl-2-(2-isopropyl-3'- methyl-l-butenyl)-cyclopropanecarboxylate. The said ethyl ester was hydrolyzedunder alkaline conditions to form dl-trans3,3-dimethyl-2-(2'-isopropyl-3-methyll-butenyl)-cyclopropane carboxylicacid having a melting point of 135C which was then reacted with thionylchloride to form dl-trans 3,3-dimethyl-2-(2'- isopropyl-3 '-methyl-l'-butenyl)-cyclopropanecarboxylic acid chloride having a boiling pointof 78 to 80C at 0.1 mm Hg.

The said acid chloride was then reacted with dl-allethrolone to formdl-trans 3,3-dimethyl-2-(2- isopropyl-3 -methyl-l -butenyl)-cyclpropanecarboxylate of dl-allethrolone having a refractive index n1.497.

EXAMPLE VIII of 96C which was then reacted with thionyl chloride to.

form dl-trans3,3-dimethyl-2-(2',6'-dimethyl-cyclohexylidene-methyl)-cyclopropanecarboxylicacid chloride having a boiling point of 104C at 0.5 mm Hg and arefractive index n 1.5020.

The said acid chloride was then reacted with dl-allethrolone to formdl-trans dimethyl-cyclohexylidene-methyl)-cyclopropane-carboxylate ofdl-allethrolone having a refractive index n 1.5136.

EXAMPLE IX PREPARATION OF dl-trans 3,3-dimethyl-2-(4',4'-di-methyl-cyclohexylidene-methyl)-cyclopropanecarboxylic acid and itsdl-allethrolone ester Using the procedure of Example I, l-bromo-2-(4,4'-dimethyl-cyclohexylidene)-ethane was reacted with sodium phenylsulfinate to form [2-(4,4-dimethyl cyclohexylidene)-ethyl]-phenylsulfone having a melting point of l C which was then reacted with methylB,B-dimethylacrylate to form methyl dl-trans 3,3-dimethyl-2-(4',4'-dimethyl-cyclohexylidene-methyl)-cyclopropanecarboxylate having a boiling point of C at 1 mm Hg. The saidmethyl ester was hydrolyzed under alkaline conditions to form dl-trans3,3-dimethyl-2-(4,4'-dimethyl-cyclohexylidenemethyl)-cyclopropanecarboxylic acid having a melting point of 96C which was then reactedwith thionyl chloride to form dl-trans 3,3-dimethyl-2-(4',4-dimethyl-cyclohexylidene-methyl)-cyclopropane carboxylic acid chloridehaving a boiling point of 1 15C at 0.7 mm Hg and a refractive index n1.5005.

EXAMPLE X PREPARATION OF dl-trans 3,3-dimethyl-2-(3, 3 ,5,5'-tetraiiriethyl-cyclohexylidene ihethyl) cyclopropane carboxylic acidand its dl-allethrolone ester Using the procedure of Example I,1-bromo-2-(3, 3 ,5 ,5 -tetramethyl-cyclohexyfideiiel ethane I W wasreacted with sodium phenyl sulfinate to form [2-(3, 3, 5 5tetramethyl-cyclohexylidene)-ethyl]-phenyl sulfone having a meltingpoint of 55C which was then reacted with ethyl B,B-dimethyl-acrylate toform ethyl dl-trans 3,3-dimethyl-2-(3',3,5',5'-tetramethylcyclohexylidene methyl)-cyclopropane carboxylate. Thesaid ethyl ester was then hydrolyzed under alkaline conditions to formdl-trans 3,3-dimethyl-2-(3',3',5',5-tetra-methyl-cyclohexylidene-methyl)- cyclopropanecarboxylic acid havinga melting point of l 16C which was then reacted with thionyl chloride toform dl-trans3,3-dimethyl-2-(3',3,5,5-tetramethylcyclohexylidene-methyl)-cyclopropane-carboxylicacid chloride having a boiling point of l 19C at 0.8 mm Hg and arefractive index n,, 1.499.

The said acid chloride was then reacted with dl-allethrolone to formdl-trans 3,3-dimethyl-2-(3',3,5',5'-tetramethyl-cyclohexylidene-methyl)- cyclopropanecarboxylate ofdl-allethrolone. 1

EXAMPLE x1 REBAwJQN. OF dl-tza a Y 3 ,5 6 tetrahydro-4pyranylidene-methyl)- cyclopropanecarboxylic acid and itsdl-allethrolone ester Using the procedure of Example I; 1-bromo-2-(2",3'. 5, 6' tetrahydro 4 pyranylidene) ethane was reacted with sodiumphenyl sulfinate to form [2-(2, 3 5', 6' tetrahydro-4-pyranylidene)-ethyl]-phenyl sulfone having a melting point of 68C whichwas then reacted with ethyl Bfi-dimethyl-acrylate to form ethyl dl-trans3,3-dimethyl-2-(2',3,5',6'-tetrahydro-4-pyranylidene-methyl)-cyclopropane carboxylate. The said ethyl ester wasthen hydrolyzed under alkaline conditions to form dl-trans3,3-dimethyl-2-(2',3,5,6'-tetrahydro-4-pyranylidene-methyl)-cyclopropanecarboxylic acid having amelting point of l02-l03C which was then reacted with thionyl chlorideto form dl-trans 3,3-dimethyl-2-(2,3,5,6'-tetrahydro-4'-pyranylidene-methyl)-cyclopropanecarboxylic acid chloride having aboiling point of 82C at 0.1 mm Hg.

The acid chloride was then reacted with dl-allethrolone to form dl-trans3,3-dimethyl-2-(2,3',5',6-tetrahydro-4'-pyranylidene-methy1)-cyclopropanecarboxylate ofdl-allethrolone having a refractive index n 1.520.

EXAMPLE XII PREPARATION OF 3-phenyl-2-(1-isobutenyl)-cyclopropanecarboxylic acid and its dl-allethrolone ester Using theprocedure of Example I, (3-methyl-2-butcnyl)-phenyl sulfone produced asin French patent No. 1,483,715 was reacted with ethyl cinnamate to formethyl 3phenyl-2 l -isobutenyl)-cyclopropanecarboxylate which washydrolyzed under alkaline conditions to form3-pheny1-2-(1'-isobutenyl)-cyc1opropanecarboxylic acid having a meltingpoint of 104C.

The said acid was reacted with thionyl chloride to form 3-phenyl-2-(1-isobuteny1)-cyclopropanecarboxylic acid chloride having a boiling pointof 101 to 103C at 0.3 mm Hg and a refractive index m, 1.5522 which wasthen reacted with dl-allethrolone to form 3-pheny1-2-(1-isobutenyl)-cyclopropanecarboxylate of dl-allethrolone having arefractive index n 1.5487.

EXAMPLE XIII Preparation of 3-methyl-2-( 1 -isobutenyl)-cyclopropane-carboxylic acid and its dl-allethrolone ester Using theprocedure of Example I, (3-methyl-2-butenyl)-p-tolyl sulfone prepared asin French patent No. 1,483,715 was reacted with ethyl crotonate to formethyl 3-methyl-2-( 1-isobutenyl)-cyclopropanecarb0xylate having aboiling point of 52C at 0.2 mm Hg and a refractive index n 1.462 whichwas hydrolyzed under alkaline conditions to form 3-methyl-2-(1-isobutenyl)-cyclopropanecarboxylic acid having a boiling point of 8182Cat 0.07 mm Hg and a refractive index n 1.4820.

The said acid .was reacted with thionyl chloride to form 3-methyl-2-(1'isobutenyl)-cyclopropanecarboxylic acid chloride having a boiling pointof 51C at 0.8 mm Hg which was then reacted with dl-allethrolone to form3-methyl-2-(1 -isobutenyl)-cyclopropanecarboxylate of dl-allethrolonehaving a boiling point of 127C at 0.01 mm Hg.

EXAMPLE XIV PREPARATION OF 3,3-dipropyl-2-(1'-isobutenyl)-cyclo-propanecarboxylic acid and its dl-allethrolone ester Using theprocedure of Example I, (3-methyl-2-butenyl)-ptolyl sulfone prepared asin French patent No. 1,483,715 was reacted with ethylB,B-dipropylacrylate to form ethyl 3,3-dipr0pyl-2-(1'-isobutenyl)cyclopropane-carboxylate having a boiling point of 9()-92C at 0.5 mm Hgand a refractive index m," 1.4660 which was hydrolyzed under alkalineconditions to form 3,3-dipropyl-2-( l "isobutenyl)-cyclopropanecarboxylic acid having a boiling point of 116C at 0.1 mm Hgand a refractive index n,, 1.4760.

The said acid was reacted with thionyl chloride to form 3,3-dipropyl-2-(l -isobutenyl)-cyclopropanecarboxylic acid chloride having a boilingpoint of 8085 C at 0.1 mm Hg and a refractive index n 1.4819

5 which was reacted with dl-allethrolone to form 3,3-

dipropyl-2-( 1 -isobutenyl)-cyclopropanecarboxylate of dl-allethrolone.

EXAMPLE XV PREPARATION OF2-(1-isobutcnyl)-spiro-[2,5loctane-l-carboxylic acid and itsdl-allethrolone ester Using the procedure of Example I,(3-mcthyl-2-butcnyl)-phenyl sulfone prepared as in French patent No.1,483,715 was reacted with ethyl cyclohexylideneacetate to form ethyl2-(1-isobutenyl)-spiro-[2,5]- octane-l-carboxylate having a boilingpoint of 9397 C at 0.7 mm Hg which was hydrolyzed under alkalineconditions to form 2-(1' isobutenyl)-spiro-[2,5]-octane-l-carboxylicacid having a melting point of 80C.

The said acid was reacted with thionyl chloride to form 2-( 1-isobutenyl)-spiro[2,5 ]-octane-1-carboxylic acid chloride having aboiling point of 7880C at 0.2 mm Hg and a refractive index n 1.5080which was reacted with dl-allethrolone to form 2-(1'-isobutenyl)-spiro-[2,5]-octane-1-carboxylate of dl-allethrolone having a refractiveindex r1 1.5193.

EXAMPLE XVI EXAMPLE XVII PREPARATION OF dl-transcyclopentylidenemethyl-cyclopropanecarboxylate cis-cinerolone esterUsing the procedure of Example I, 1.15 gm of ditrans3,3-dimethyl-2-cyclopentylidenemethylcyclopropanecarboxylic acidchloride produced in Step D of Example IV was reacted with 0.9 gm ofciscinerolone to form 1.24 gm of dl-trans 3,3-dimethyl-2- 55cyclopentylidene-methyl-cyclopropanecarboxylate of cis-cinerolone havinga refractive index n 1.5179.

EXAMPLE XVIII Preparation of dl-trans 3,3-dimethyl-2-cyclopentylidenemethyl-cyclopropanecarboxylate of 1-oxo-3-methyl-2-(2'cyclohexenyl)-2-cyclopentene-4-o1 Using the procedure ofExample I dl-trans 3,3-dimethyl-2-cyclopentylidenemethyl-cyclopropanecar- 65 boxylic acidchloride produced as in Step D of Example IV was reacted with1-oxo-3-methyl-2-(2'-cyclohexenyl)-2-cyclopentene-4-ol (Coll. Czech.Vol. 25, 1960, p. 1835) to form dl-trans 3,3-dimethyl-2-cyclopenty-3,3-dimethy1-2- lidenemethyl-cyclopropanecarboxylate of l-oxo-3-methyl-2-(2'-cyclohexenyl)-2-cyclopentene-4-ol having a refractive indexof 11,, 1.523.

EXAMPLE XIX PREPARATION OF dl-trans 3,3-dimethyl-2-cyclobutylidenemethyl-cyclopropanecarboxylate of dlallethrolone Usingthe procedure of Example I, 1-bromo-2- cyclobutylidene-ethane wasreacted with sodium phenyl sulfinate to form(2-cyclobutylidene-ethyl)-phenyl sulfone having a melting point of 76 to78C which was then reacted with ethyl B,B-dimethylacrylate to form ethyldl-trans 3,3-dimethyl-2-cyclobutylidenemethylcyclopropanecarboxylate.The said ethyl ester was hydrolyzed under alkaline conditions to formdl-trans 3,3-dimethyl-2-cyclobutylidenemethyl-cyclopropanecarboxylicacid.

The said acid was reacted with thionyl chloride to form dl-trans3,3-dimethyl-2-cyclobutylidenemethylcyclopropane-carboxylic acidchloride which was then reacted with dl-allethrolone to form dltrans3,3- dimethyl-2-cyclobutylidene-methyl-cyclopropanecarboxylate ofdl-allethrolone. The compounds obtained at the different steps of theexamples V1 to XlX are not described in the literature.

EXAMPLE XX PREPARATION OF dl-cis and trans2,2,5-trimethylspiro-[2,5]-4-octene-l-carboxylic acids and the transacidester with dl-allethrolone.

Step A: Preparation of (3-methyl-2-cyclohexenyl)- phenyl sulfone 34.2 gmof raw 3-methyl-2-cyclohexene-l-ol were introduced into 400 cc of formicacid and then 68 gm of sodium phenyl sulfinate were added thereto. Themixture was agitated for 15 hours at room temperature and then waspoured into a water-ice mixture. Next, the reaction mixture wasextracted with methylene chloride and the methylene chloride extractswere combined, washed first with water, then with an aqueous solution ofsodium bicarbonate and again with water, then dried and concentrated todryness. The residue was admixed with a mixture of isopropyl ether andpetroleum ether and the resultant precipitate was isolated byfiltration, washed and dried to obtain 47 gm of(3-methyl-2-cyclohexenyl)-phenyl sulfone. A sample of this product waspurified by dissolution in methylene chloride, concentration thereof andan addition of isopropyl ether to obtain the said sulfone having amelting point of 70C.

Analysis: C H O S; molecular weight 236.33 Calculated:'C:66.06% H:6.82%S:13.57% Found: C:66.3% H:6.8% S:13.3%

This product is not described in the literature.

Step B: Preparation of ethyl dl-cis and trans 2,2,5-trimethyl-spiro-[2,5 ]-4-octenel -carboxylate a. First, 9.5 g of potassiumtert.-butylate, then 10 gm of (3-methyl-2-cyclohexenyl)-phenyl sulfonewere introduced into 50 cc ofdimethylsulfoxide containing 1.5 percent ofwater, 9.5 cc of ethyl B,B-dimethylacrylate were added over about 5minutes and the mixture was agitated for 1 hour at room temperature.Then the reaction mixture was cooled to 0C and acidified with a diluteaqueous solution of hydrochloric acid. The aqueous phase was extractedwith methylene chloride and the methylene chloride extracts werecombined. The organic solution obtained was washed first with an aqueoussolution of sodium bicarbonate, then with water, dried and concentratedto dryness under pressure to obtain 8.8 gm of substantially pure ethyldltrans 2,2,5-tri-methyl-spiro-[2,5]-4-octene-l-carboxylate.

This product is not described in the literature.

b. The same method as described above was repeated but dimethylsulfoxidecontaining 1.5 percent of water was replaced with dimethylsulfoxidecontaining 0.08 percent of water to obtain substantially pure ethyldl-cis 2,2,5-trimethyl-spiro-[2,5]-4-octene-l-carboxylate.

This product is not described in the literature.

Step C: a. Preparation of dl-trans 2,2,5-trimethyl-spiro- [2,5]-4-octenel -carboxylic acid One cc of water and 8.8 gm of ethyldl-trans 2,2,5- trimethyl-spiro-[2,5]-4-octene-l-carboxylate wereintroduced into a mixture of 20 cc of methanol and 30 cc of a 2 Nmethanolic sodium hydroxide solution under an atmosphere of nitrogen.The mixture was brought to reflux and maintained at reflux for 1 hour.Then the methanol was eliminated by distillation and the remainder wasdiluted with water. The aqueous phase was extracted with ethyl ether andthe ether extracts were combined and washed with water. The ethersolution, which contained as undesired neutral fraction, was eliminated.All of the aqueous phases were acidified with a dilute aqueous solutionof hydrochloric acid and then were extracted with methylene chloride.The methylene chloride extracts were combined, washed with an aqueoussolution of sodium chloride, dried and concentrated to dryness. Theresidue was admixed with isopropyl ether and the precipitate formed wasisolated by vacuum filtering and dried to obtain the desired dl-trans2,2,5-trimethyl-spiro-[2,5]-4-octene-1- carboxylic acid having a doublemelting point: 122C, then 130-132C.

Analysis: C H O molecular weight 194.26 Calculated: C 74.19%; H:9.33%;Found: C: 74.4%; H: 9.3%;

The R. M. N. spectra of this product showed an ethylenic proton at 288Hz which is characteristic of the trans isomer. This product is notdescribed in the literature.

b. Preparation of dl-cis 2,2,5-trimethyl-spiro-[2,5 ]-4- octenel-carboxylic acid By starting with ethyl dl-cis 2,2,5-trimethyl-spiro-[2,51-4-octene-l-carboxylate and using the same procedure as describedfor the preparation of trans acid, the dl-cis2,2,5-trimethyl-spiro-[2,5]-4-octene-lcarboxylic acid was obtainedhaving a melting point of l40l42C after recrystallization from isopropylether.

Analysis: C, H, O molecular weight 194.26 Calculated: C:74.l9%; H:9.33%Found: C: 74.3%; H: 9.4%

The R. M. N. spectra os this product showed an ethylenic proton at 322Hz which is characteristic of the cis isomer. This product is notdescribed in the literature.

Step D: Preparation of dltrans 2,2,5-trimethyl-spiro- [2,5]-4octene-1-carboxylic acid chloride 2.5 gm of dl-trans2,2,S-trimethyl-spiro-[2,5]-4-octene-lcarboxylic acid were introducedinto a mixture of 15 cc of petroleum ether (boiling point 30-70C) and ccof benzene. Next, 1.4 cc of thionyl chloride were added dropwise and themixture was agitated for 1 hour at room temperature and then at 60C for20 minutes. Thereafter, 1.4 cc of thionyl chloride were added, and thereaction mixture was agitated for 2 hours and 30 minutes at roomtemperature. The solvent and the excess thionyl chloride were eliminatedby distillation under vacuum.

The residue was rectified under vacuum to obtain 0.836 gm of dl-trans2,2,5-trimethyl-spiro-[2,51-4-octene-l-carboxylic acid chloride having aboiling point of 80C under 0.5 mm pressure of mercury and it wasutilized as such for the next step.

This product is not described in the literature. Step E: Preparation ofdl-trans 2,2,5-trimethyl-spiro- [2,5]-4-octene-l -carboxylate ofdl-allethrolone One cc of pyridine and 0.836 gm of dl-trans 2,2,5-trimethyl-spiro-[2,5 ]-4-octene-l -carboxylic acid chloride wereintroduced into 5 cc of benzene. and then a solution of 0.600 gm ofdl-allethrolone in 4 cc of benzene was added dropwise. The mixture wasagitated for 16 hours at room temperature. Thereafter, the precipitateformed was eliminated by filtration and the benzene filtrate wassuccessively washed with a dilute aqueous solution of hydrochloric acid,with water, with an aqueous solution of sodium bicarbonate and againwith water. The solution was dried over magnesium sulfate andconcentrated to dryness. The residue was dissolved in cyclohexane andthe solution obtained was passed through an alumina column to obtain0.981 gm of dl-trans 2,2,5-trimethyl-spiro-[2,51-4-octene-l-carboxylateof dl-allethrolone. Analysis: C H O molecular weight 328.43 Calculated:C:76.79%; H:8.59% Found: C: 76.7%; H: 8.3

This product is not described in the literature.

EXAMPLE XXI PREPARATION OF dl-trans 3,3-dimethyl-2-cyclopropylidene-methyll -cyclopropanecarboxylic acid and itsdl-allethrolone ester Step A: Preparation of dl-transcyclopropylidenemethyl-l -cyclopropane acid Twenty-four gm ofcyclopropyl triphenyl phosphonium bromide and 5 gm of a suspensioncontaining 50 percent of sodium hydride in vaseline oil were introducedinto 100 cc of dimethoxyethane. The reaction mixture was heated toreflux and maintained at reflux for minutes after which a mixture of5.92 gm of dltrans caronaldehydic acid and 30 cc of dimethoxyethane wereadded dropwise. The reaction mixture was held at reflux for 1 hour and30 minutes and then cooled. The insoluble substance formed waseliminated by filtration and the filtrate was concentrated to drynessunder reduced pressure. Water was added to the residue and the insolublematter formed was eliminated by filtration. This filtrate was acidifiedwith a dilute solution of hydrochloric acid and the. aqueous acid phasewas extracted with ether. The ether extracts were combined, washed withan aqueous saturated solution of sodium chloride, then dried,decolorized with animal charcoal and finally concentrated to drynessunder reduced pressure to obtain a partially crystallized product. Thecrystals were separated from the oily portion by vacuum filtering overfritted glass. The product 3,3-dimethyl-2- carboxylic thus isolated wasrecrystallized from isopropyl ether to obtain 2.74 gm of dl-trans3,3-dimethyl-2-cyclopropylidenemethyl-l-cyclopropanecarboxylic acidhaving a melting point of C.

By starting with the filtrate and the mother liquors of isopropyl ethercrystallization and esterification with diazomethane, purification ofthe product obtained by chromatography and saponification gave a secondyield of 0.555 gm of the same acid having a melting point of 84-85C. Asample of this product after recrystallization from isopropyl ether hada melting point of C. Analysis: C H O molecular weight 166.21Calculated: C: 72.26%; H: 8.48%

Found: C: 72.0%; H: 8.5

By ozonization of this compound in a chloroform, media, followed bydecomposition of the ozonide in oxidizing media hydrogen peroxide, thetrans caronic acid was obtained (melting point 212C), which establishedthe trans structure of the starting cyclopropanecarboxylic acid. Thisstructure was, furthermore, confirmed by the R. M. N. spectra of thecompound which had a doublet at 96l0l.5 Hz corresponding to the protonin the 1-position of the cyclopropane ring and of which the couplingconstant with the proton in the 2-position ('r 5.5 Hz.) corresponded toa trans structure.

This dl-trans3,3-dimethyl-2-cyclopropylidenemethyl-l-cyclopropanecarboxylic acid isnot described in the literature.

Step B: Preparation of dl-trans 3,3-dimethyl-2- cyclopropylidenemethyll-cyclopropanecarboxylic acid chloride 1.1 gm of dl-trans3,3-dimethyl-2-cyclopropylidenemethyl-l-cyclopropanecarboxylic acid wereintroduced into 5 cc of benzene and 0.55 cc of thionyl chloride wereadded over about 15 minutes. Next, the reaction mixture was agitated for3 hours at room temperature, after which the solvent and the excessthionyl chloride were eliminated by distillation under reduced pressureto obtain 1.2 gm of raw dl-trans 3,3-dimethyl-2-cyclopropylidenemethyl-l-cyclopropanecarboxylic acid chloride. Theproduct was utilized as such for the next step.

This compound is not described in the literature. Step C: PREPARATION OFdl-trans 3,3-dimethyl-2- cyclopropylidenemethyll-cyclopropanecarboxylate of dl-allethrolone First, 1.2 gm of dl-trans3,3-dimethyl-2-cyclopropylidenemethyl-l-trans cyclopropanecarboxyli'cacid chloride, then 1.05 gm of dl-allethrolone in solution in 8 cc ofbenzene were introduced into a mixture of 5 cc of benzene and 1.3 cc ofpyridine and the reaction mixture was agitated for 15 hours at roomtemperature. Then the precipitate formed was eliminated by filtrationand the organic filtrate was washed successively, with a dilute aqueoussolution of hydrochloric acid, with an aqueous solution of sodiumchloride, with an aqueous solution of sodium bicarbonate and lastlyagain with an aqueous solution of sodium chloride. After having beendried, the solution was concentrated to dryness under reduced pressure.Then the residue was subjected to chromatography through alumina toobtain 1.46 gm of dl-trans3,3-dimethyl-2-cyclopropylidenemethyl-l-cyclopropanecarboxylate ofdl-allethrolone having a refractive index n 1.521. Analysis: C,. ,l-l.,O molecular weight 300.38

Calculated: C:75.97%; H:8.05% Found: C: 75.8%; H: 8.1 UltravioletSpectra (in ethanol) A max. 223-224 m (e 18,200)

The R. M. N. spectra of this compound showed at 97.5403 Hz, a doubletwhich corresponded to the proton in the l-position of the cyclopropanering. The coupling constant of this proton and of the proton in the2-position (r 5.5 Hz), had, therefore, a value characteristic of thetrans structure.

This compound is not described in the literature.

EXAMPLE XXII Preparation of dl-trans3,3-dimethyl-2-cyclobutylidene-methyll-cyclopropanecarboxylic acid andits dlallethrolone ester Step A: Preparation of dl-trans 3,3-dimethyl-2-cyclobutylidenemethyl- 1 -cyclopropanecarboxylic acid.

5.84 gm of a 50% sodium hydride suspension in vaseline oil and 28.5 gmof cyclobutyl triphenyl phosphonium bromide were introduced into 300 ccof dimethoxyethane under an atmosphere of nitrogen. The reaction mixturewas brought to reflux and held at reflux for 40 minutes. Then a solutionof 6.8 gm of dltrans caronadelhydic acid in 25 cc of dimethoxyethane wasadded thereto over about 15 minutes. The reaction mixture was again heldat reflux for 30 minutes. The precipitate formed was eliminated byfiltration and the filtrate was concentrated to dryness. Water was addedto the residue and the precipitate formed was removed by filtration andwashed with water. The combined aqueous phases were extracted with etherand the aqueous solution was acidified with a dilute aqueous solution ofhydrochloric acid. The aqueous acid solution was extracted with etherand the acid ether extracts were combined, washed with water, dried andconcentrated to dryness. The residue was crystallized first fromisopropyl ether, then from ether to obtain 4.84 gm of dl-trans3,3-dimethyl-2-cyclobutylidenemethyl-l-cyclopropanecarboxylic acidhaving a melting point of 98C.

Analysis: c,,H,,o,; molecular weight 180.24 Calculated: C: 73.30% H:8.95% Found: C: 73.1% H: 9.0%

The R. M. N. spectra of this compound showed at 82-87 Hz a doublet whichcorresponded with the proton in' the l-position of the cyclopropanering. The coupling constant of this proton and of the proton in the2-position ('r 5 Hz) had, therefore, a value characteristic of the transformation.

This compound is not described in the literature. Step B: Preparation ofdl-trans 3,3-dimethyl-2-cyclobu tylidenemethyll -cyclopropanecarboxylicacid chloride Under an atmosphere of nitrogen, 2 gm of dl-trans3,3-dimethyl-2-cyclobutylidenemethylcyclopropanecarboxylic acid weresuspended in cc of petroleum ether, (boiling point 5070C) and then 1.2cc of thionyl chloride were added to the reaction mixture which was thenagitated for minutes at room temperature. The solvent and the excessthionyl chloride were eliminated by distillation under vacuum and theresidue was rectified to obtain 1.88 gm of dltrans3,3-dimethyl-2-cyclobutylidene-1- cyc lopropanecarboxylic acid chloridehaving a boiling polpt of 85C at 0.7 mm Hg and a refractive index n1.5090. The product was utilized as such for the next step.

This compound is not described in the literature. Step C: Preparation ofdl-trans 3,3-dimethyl2-cyclobutylidenemethyl-l-cyclopropanecarboxylateof dl-allethrolone 1.885 gm of dl-trans3,3-dimethyl-2-cyclobutylidenemethyl-l-cyclopropanecarboxylic acidchloride were introduced into 5 cc of benzene and then a solution of1.46 gm of dl-allethrolone in a mixture of 2 cc of pyridine and 10 cc ofbenzene was added dropwise. Next, the reaction mixture was agitated for15 hours at room temperature and a few drops of formic acid were addedthereto and the reaction mixture was then diluted with water. Theorganic phase was separated by decanting and the aqueous phase wasextracted with ether. The ether extracts were combined with theprincipal organic phase and the organic solution obtained was washedsuccessively with a dilute aqueous solution of hydrochloric acid, withwater with a aqueous solution of sodium bicarbonate and again withwater. The solution was dried and concentrated to dryness and theresidue was dissolved in benzene. Then the solution was passed throughan alumina column and the eluate was concentrated to dryness to obtain2.74 gm of dltrans 3 ,3-dimethyl-2-cyclobutylidenemethyl-1-cyclopropane-carboxylate of dl-allethrolone having a refractive index n1.5192.

Analysis: C H O molecular weight 314.41 Calculated: C: 76.40%; H: 8.34%Found: C: 76.1%; H: 8.4% Ultraviolet Spectra (in ethanol) A max. 224-225mi (6 21,200) This compound is not described in the literature.

EXAMPLE XXlll PREPARATION OF (5-benzyl-l-furyl-3 )-methyl dltrans3,3-dimethyl-2-cyclopentylidenemethyl-lcyclopropanecarboxylate Step A:Preparation of dl-trans 3,3-dimethyl-2- cyclopentylidenemethyl- 1-cyclopropanecarboxylic acid chloride 1. Preparation of the sodium saltof the acid 1.08 gm of dl-trans 3,3-dimethyl-2-cyclopentylidenemethyl-1-cyclopropanecarboxylic acid was dissolved in 10 cc of methanolcontaining 10 percent water and then sodium methylate was added untilalkaline reaction.

Next the methanol was eliminated by distillation under vacuum andbenzene was added and the mixture was again distilled in order tocompletely eliminate the water of the reaction whereby the sodium saltof dltrans 3,3-dimethyl 2-cyclopentylidenemethyll cyclopropanecarboxylicacid was obtained.

This compound is not described in the literature.

2. Preparation of the acid chloride The sodium salt obtained in thepreceding step was suspended in 30 cc of benzene and the reactionmixture was cooled after which 2 cc of pyridine, followed by 4.7 cc ofoxalyl chloride were added thereto. Next the reaction mixture wasagitated and the precipitate formed was eliminated by filtration andwashed with benzene. The benzene wash liquors were combined with theprincipal filtrate to obtain a benzene solution of dl-trans3,3-dimethyl-2-cyclopentylidenemethyl-1- cyclopropanecarboxylic acidchloride which was used as such for the next step.

Step B: Preparation of (5-benzyl-furyl-3)-methyl dltrans 3,3-dimethyl-2-cyclopentylidene-methyl-1- cyclopropane carboxylate.

1.5 cc of pyridine and 1.05 gm of (5-benzyl-furyl-3)- methyl alcohol ina solution in 10cc of benzene were added to the benzene solution of theacid chloride obtained in the preceding. The reaction mixture wasagitated for 16 hours at room temperature and then water was added. Theorganic phase was separated by decanting. The aqueous phase wasextracted with ether and the combined organic phases were washedsuccessively with a cold aqueous solution of hydrochloric acid, withwater, with an aqueous solution of sodium bicarbonate and again withwater, dried and concentrated to dryness. The product thus obtained wasdissolved in benzene and the benzene solution was passed through analumina column and the eluate was concentrated to dryness to obtain1.234 gm of(S-benzyl-furyl- 3 )-methyl dl-trans 3,3-dimethyl-2-cyclopentylidenemethyl-1-cyclo-propanecarboxylate having amelting point below 40C. The product was in solid form at roomtemperature. Analysis: C d-1 molecular weight 364.46 Calculated: C:79.09%; H: 7.74% Found: C: 79.4%; H: 8.0% Ultraviolet Spectra (inethanol) )t max. at 207 208 mu (e= 24,000)

This compound is not described in the literature.

EXAMPLE XXIV PREPARATION OF (5-benzyl-furyl-3 )-methyl dltrans 3,3-dimethyl-2-cyclopentylidenemethyl-1- cyclopropanecarboxylate Step A:Preparation of d-trans 3,3-dimethyl-2- cyclopentylidenemethyl- 1-cyclopropanecarboxylic acid lephedrine was reacted with dl-trans3,3-dimethyl- 2-cyclopentylidenemethyll -cyclopropanecarboxylic acid inthe presence of ethyl acetate. A precipitate was isolated by vacuumfiltration which, after purification, led to the lephedrine salt ofd-trans 3,3-dimethyl-2- cyclopentylidene-methyl-1-cyclopropanecarboxylicacid (salt A) having a melting point of 162C and a specific rotation of[111 =7 (c 1.1 percent in chloroform).

By acidification of salt A, d-trans 3,3-dimethyl-2-cyclopentylidenemethyll -cyclopropanecarboxylic acid having a meltingpoint of 60C (slightly pure) and a specific rotation of [01],, 2 (0 1percent in chloroform) (acid A,) was obtained.

From the filtrate(ethyl acetate solution) 'a product was obtained which,after purification, was the lephedrine .salt of l-trans3,3-dimethyl-2-cyclopentylidene-methyl-l-cyclopropanecarboxylic acid(salt B) having a melting point of 1 12C and a specific rotation of[a],,"=1 3 (c= 1.1 percent in chloroform).

By acidification of salt B, l-trans 3,3-dimethyl-2-cyclopentyIidenemethyl-l-cyclopropanecarboxylic acid having a meltingpoint of 60C and a specific rotation of [11],, 0 (0 1 percent inchloroform) (acid 8,) was obtained.

Although the rotatory power of the acids obtained 32 The lephedrine saltof d-trans 3,3-dimethyl-2- cyclopentylidenemethyll-cyclopropanecarboxylic acid, the lephedrine salt of l-trans3,3-dimethyl-2- cyclopentylidene-methyl-1-cyclopropanecarboxylic acid,d-trans 3,3-dimethyl-2-cyclopentylidenemethyl-1 -cyclopropanecarboxylicacid and l-trans 3,3- dimethyl-2-cyclopentylidenemcthyl-l-cyclopropanccarboxylic acid are not described in the literature. Step B: Preparationof d-trans 3,3-dimethyl-2- cyclopentylidenemethyl-said acid.

-cycl0propanecarboxylic acid chloride 1. Preparation of the sodium saltof the saidl .14 gm of d-trans3,3-dimethyl-2-cyclopentylidenemethyl-l-cyclopropanecarboxylic acid weredissolved in 2 cc of methanol and then sufficient 2.06 N methanolicsodium hydroxide solution was added until alkaline reaction. Themethanol was eliminated under reduced pressure and benzene was added tothe residue and the solution was again concentrated to dryness underreduced pressure in order to entirely eliminate the water of thereaction whereby the sodium salt of d-trans 3,3-dimethyl-2-cyclopentylidenemethyl-1- cyclopropane carboxylic acid wasobtained. This compound is not described in the literature. 2.Preparation of the acid chloride The sodium salt obtained in thepreceding step was suspended in 30 cc of benzene and the reactionmixture was cooled. Under an atmosphere of nitrogen, first 2 cc ofpyridine, then 4.7 cc of oxalyl chloride were added to the reactionmixture which was then agitated and concentrated to dryness underreduced pressure. Then benzene was added to the residue and the reactionmixture was again concentrated to dryness to entirely eliminate thebenzene and oxalyl chloride. The precipitate formed was removed byfiltration and was washed with benzene and the benzene wash waters werecombined with the principal filtrate to obtain a benzene solution ofd-trans 3,3-dimethyl-2-cyclopentylidenemethyll-cyclopropanecarboxylicacid chloride which was utilized as such for the next step. Step C:Preparation of (5-benzyl-furyl-3 )-methyl dtrans 3,3-dimethyl-2-cyclopentylidenemethyl-1- cyclopropanecarboxylate.

Two cc of pyridine and 1.12 gm of(5-benzyl-furyl-3) methyl alcohol insolution in 10 cc of benzene were i added to the benzene solution ofd-trans acid chloride may border on zero, resolution had definitelyoccurred.

In fact, by ozonization of d-trans chrysanthemic acid as well as byozonization of acid A obtained from the ephedrine salt having a meltingpoint of 162C, the

same l-trans caronic acid was arrived at having a melting point of 212Cand a specific rotation of [01],, 35 (0 1.8 percent in methanol). [See11. Staudinger and L. Ruz'icka, Helv. Chem. Acta 7, 201 (1924)].

of Step B and the reaction mixture was agitated for 16 hours at roomtemperature and then diluted with water. The organic phase was separatedby decanting and the aqueous phase was extracted with ether and theether phases were combined with the benzene solution. The organic phaseobtained was washed successively with a cold aqueous solution ofhydrochloric acid, with water, with an aqueous solution of sodiumbicarbonate and again with water, then dried and concentrated todryness. The residue was dissolved in benzene and the benzene solutionobtained was passed through an alumina column and the eluate wasconcentrated to dryness to obtain 1.3 gm of (5-benzyl-furyl-3)-methyldtrans 3,3-dimethyl-2-cyclopenty1idenemethyl-1- cyclopropanecarboxylatehaving a refractive index n,,' 1.5420.

Analysis: C H O molecular weight 364.46

Calculated: C: 79.09%; H: 7.74% Found: C: 79.1%; H: 7.7%

Ultraviolet Spectra (in ethanol) A max. at 208 mp,( 6 23,500) Thiscompound is not described in the literature.

Various modifications of the process of the invention may be madewithout departing from the spirit or scope thereof and it is to beunderstood that the invention is to be limited only as defined in theappended claims.

We claim:

1. An aryl allyl sulfone of the formula H-ASAr wherein Ar is phenyloptionally substituted with a substituent selected from the groupconsisting of lower alkyl, lower alkoxy, halo methyl, halogen and nitroand H A has the formula wherein R is selected from the group consistingof hydrogen and lower alkyl, and R and R taken together with the carbonatom to which they are attached form a radical selected from the groupconsisting of fluorene and saturated and unsaturated cycloalkyl of threeto seven carbon atoms optionally substituted with one to twosubstituents selected from the group consisting of lower alkyl and loweralkoxy.

2. A compound of claim 1 which is (2-cyclopentylidene ethyl)-phenylsulfone.

3. A compound of claim 1 which is (2-cyclohexylidene-ethyl)-phenylsulfone.

4. A compound of claim 1 which is [2-(2',6- dimethyl-cyclohexylidene)ethyl]-phenyl sulfone.

5. A compound of claim 1 which is [2-(4,4'-dimethyl-cyclohexylidene)-ethyl]-phenyl sulfone.

6. A compound of claim 1 which is [2-(3,3',5,5'-tetramethyl-cyclohexylidene)-ethyl]-phenyl sulfone.

7. A compound of claim 1 which is [2-cyclobutylideneethyl]-phenylsulfone.

2. A compound of claim 1 which is (2-cyclopentylidene ethyl)-phenylsulfone.
 3. A compound of claim 1 which is(2-cyclohexylidene-ethyl)-phenyl sulfone.
 4. A compound of claim 1 whichis (2-(2'' ,6''-dimethyl-cyclohexylidene)-ethyl)-phenyl sulfone.
 5. Acompound of claim 1 which is (2-(4'',4''-dimethyl-cyclohexylidene)-ethyl)-phenyl sulfone.
 6. A compound ofclaim 1 which is (2-(3'' ,3'' ,5'',5''-tetramethyl-cyclohexylidene)-ethyl)-phenyl sulfone.
 7. A compoundof claim 1 which is (2-cyclobutylidene-ethyl)-phenyl sulfone.